tbuckley/cabot-search huggingface dataset:
Abstract 9689: Impact of Epinephrine Administration Route on the Outcomes of Cardiac Resuscitation of Acute Myocardial Infarction Patients With Cardiac Arrest in the Cardiac Catheterization Laboratory (iCPR Study)
Authors: Ayman Haq, Ali Aldujeli, Kristen M Tecson, Karolis Lickunas, Ramunas Unikas, Anas Hamadeh, Emmanouil S Brilakis
Journal: Circulation (2022)

Objectives: To compare the efficacy peripheral intravenous (IV), central IV, and intracoronary (IC) administration of epinephrine in acute myocardial infarction (AMI) patients with cardiac arrest in the cath lab. Methods: Prospective, two-center cohort pilot study of AMI patients with cardiac arrest in the cath lab. Patients who received mechanical circulatory support, primary fibrinolysis, anti-arrhythmic/vasopressors prior to cardiac arrest, or those with prior CAD or a cardiac arrest that lasted &lt; 60 seconds were excluded. Outcomes included return of spontaneous circulation (ROSC), stent thrombosis, and survival-to-discharge with a favorable neurological outcome. Results: 158 patients were enrolled (Table 1). After adjusting for age and initial cardiac rhythm, the peripheral IV route had 5.5-fold lower odds (OR: 0.18, 95% CI: 0.07-0.49, p = 0.0007) of achieving ROSC compared with the central IV route, while the IC route had a similar odds compared to the central IV route ( p = 0.9516). Among those who achieved ROSC, the IC route had a higher odds for stent thrombosis compared to the central IV route (OR: 5.7, 95% CI: 1.9-17.2, p = 0.0022), but not the peripheral IV route ( p = 0.1277). The adjusted odds of achieving survival-to-discharge with a favorable neurological outcome were higher in the IC route compared to the peripheral IV route (OR: 7.8, 95% CI: 2.2 – 27.0, p = 0.0013), and similar in the IC and central IV routes ( p = 0.0585) (Table 2). Conclusions: Epinephrine administration via central IV has a higher odds achieving ROSC than via peripheral IV and a lower odds of stent thrombosis than via the IC route in patients with AMI who suffer from cardiac arrest during PCI.
Rare, convergent antibodies targeting the stem helix broadly neutralize diverse betacoronaviruses
Authors: Cherrelle Dacon, Linghang Peng, Ting-Hui Lin, Courtney Tucker, Chang-Chun D. Lee, Yu Cong, Lingshu Wang, Lauren Purser, Andrew J.R. Cooper, Jazmean K. Williams, Chul-Woo Pyo, Meng Yuan, Ivan Kosik, Zhe Hu, Ming Zhao, Divya Mohan, Mary Peterson, Jeff Skinner, Saurabh Dixit, Erin Kollins, Louis Huzella, Donna Perry, Russell Byrum, Sanae Lembirik, Michael Murphy, Yi Zhang, Eun Sung Yang, Man Chen, Kwanyee Leung, Rona S. Weinberg, Amarendra Pegu, Daniel E. Geraghty, Edgar Davidson, Benjamin J. Doranz, Iyadh Douagi, Susan Moir, Jonathan W. Yewdell, Connie Schmaljohn, Peter D. Crompton, John R. Mascola, Michael R. Holbrook, David Nemazee, Ian A. Wilson, Joshua Tan
Journal: Cell Host & Microbe (2023)

(Cell Host & Microbe 31, 97–111.e1–e12; January 11, 2023) In Figure 6A, the authors discovered after publication that the neutralization NT50 values of two similar IGHV1-46/IGKV3-20 mAbs (COV30-14 and COV72-37) for several SARS-CoV-2 variants were switched due to a copying error. This correction does not impact the conclusions of the original paper. The affected NT50 values of the two mAbs only differed <2 fold. The authors regret the inconvenience caused by this error, which has been corrected in the original article online. Rare, convergent antibodies targeting the stem helix broadly neutralize diverse betacoronavirusesDacon et al.Cell Host & MicrobeNovember 7, 2022In BriefThe characteristics of antibodies that broadly neutralize coronaviruses are poorly understood. Here, Dacon et al. identify a class of stem helix-specific monoclonal antibodies from COVID-19 convalescent donors that neutralize diverse betacoronaviruses, use an IGHV1-46/IGKV3-20 gene signature, and bind in a conserved manner to the spike protein. Full-Text PDF Open Access
Multitraction with a single rubber band and clips: a simple tip for endoscopic submucosal dissection of a recurrent lesion with previous clip
Authors: Marion Schaefer, Jérémie Albouys, Sophie Geyl, Romain Legros, Mathieu Pioche, Jean-Baptiste Chevaux, Jérémie Jacques
Journal: Endoscopy (2023)

Endoscopic submucosal dissection (ESD) with double-clip traction (DCT) with a rubber band and two clips allows excellent en bloc and curative resection rates and is probably the cheapest traction system available [1]. Incomplete previous resection or recurrence is associated with a higher piecemeal resection rate [2] and severe fibrosis is an independent predictor of perforation [3]. DCT is also safe and effective in these settings [4]. Multipolar traction has been reported to improve the visualization of the submucosa with four peripheral rubber bands fixed with four clips on the edges and attached to a central band that is fixed on the opposite wall with a fifth clip [5]. This is effective but requires some time to set up the device, which can be difficult to advance up through a thin operative channel.
Management of rare biliary duct variants using a nasobiliary drainage tube and wire-guided navigation during laparoscopic cholecystectomy: a case report
Authors: Cheng Zhang, Yun-sheng Suo, Sheng-long Zhang, Ke Sun, Yang He, Guang-kuo Li
Journal: Endoscopy (2023)

Biliary anatomical variation is an important risk factor for bile duct injury during laparoscopic cholecystectomy [1]. In the present case, we used a nasobiliary drainage tube and wire-guided navigation to identify a rare biliary variant and provide intraoperative guidance to reduce the risk of bile duct injury during laparoscopic cholecystectomy ([Video 1]).
Tackling tack removal after use of the through-the-scope helix tack and suture device for stent fixation
Authors: Natalie Wilson, Mohamed Abdallah, Eric M. Pauli, Mohammad Bilal
Journal: Endoscopy (2023)

The through-the scope (TTS) helix tack-and-suture device (X-Tack; Apollo Endosurgery, Austin, Texas, USA) is a newer endoscopic suturing device used for closure of large defects after endoscopic resection [1] [2]. This device has recently been gaining popularity as a tool for stent fixation [1] [3] [4]. One of the limitations of this device for stent fixation is the lack of a dedicated removal tool. Here, we demonstrate two options for helical tack removal following application for stent fixation.
TFEB is a central regulator of the aging process and age-related diseases
Authors: Samuel Abokyi, George Ghartey-Kwansah, Dennis Yan-yin Tse
Journal: Ageing Research Reviews (2023)

Old age is associated with a greater burden of disease, including neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, as well as other chronic diseases. Coincidentally, popular lifestyle interventions, such as caloric restriction, intermittent fasting, and regular exercise, in addition to pharmacological interventions intended to protect against age-related diseases, induce transcription factor EB (TFEB) and autophagy. In this review, we summarize emerging discoveries that point to TFEB activity affecting the hallmarks of aging, including inhibiting DNA damage and epigenetic modifications, inducing autophagy and cell clearance to promote proteostasis, regulating mitochondrial quality control, linking nutrient-sensing to energy metabolism, regulating pro- and anti-inflammatory pathways, inhibiting senescence and promoting cell regenerative capacity. Furthermore, the therapeutic impact of TFEB activation on normal aging and tissue-specific disease development is assessed in the contexts of neurodegeneration and neuroplasticity, stem cell differentiation, immune responses, muscle energy adaptation, adipose tissue browning, hepatic functions, bone remodeling, and cancer. Safe and effective strategies of activating TFEB hold promise as a therapeutic strategy for multiple age-associated diseases and for extending lifespan.
Development of a novel colorectal endoscopic submucosal dissection training model
Authors: Tomohiro Mitsui, Hironori Sunakawa, Seiichiro Takayama, Tatsuro Murano, Kensuke Shinmura, Hiroaki Ikematsu, Tomonori Yano
Journal: Endoscopy (2023)

Colorectal endoscopic submucosal dissection (ESD) requires technically advanced endoscopic skill. To improve endoscopic skills, animals or their extracted digestive tracts are used for ESD training [1] [2] [3], which raises several issues regarding ethics, cost, and infection.
Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning
Authors: Caelan E. Radford, Philipp Schommers, Lutz Gieselmann, Katharine H.D. Crawford, Bernadeta Dadonaite, Timothy C. Yu, Adam S. Dingens, Julie Overbaugh, Florian Klein, Jesse D. Bloom
Journal: Cell Host & Microbe (2023)

Understanding the specificities of human serum antibodies that broadly neutralize HIV can inform prevention and treatment strategies. Here, we describe a deep mutational scanning system that can measure the effects of combinations of mutations to HIV envelope (Env) on neutralization by antibodies and polyclonal serum. We first show that this system can accurately map how all functionally tolerated mutations to Env affect neutralization by monoclonal antibodies. We then comprehensively map Env mutations that affect neutralization by a set of human polyclonal sera that neutralize diverse strains of HIV and target the site engaging the host receptor CD4. The neutralizing activities of these sera target different epitopes, with most sera having specificities reminiscent of individual characterized monoclonal antibodies, but one serum targeting two epitopes within the CD4-binding site. Mapping the specificity of the neutralizing activity in polyclonal human serum will aid in assessing anti-HIV immune responses to inform prevention strategies.
Abstract 9234: Evaluating the Association Between Perceived Discrimination and Health Status Outcomes Among Young Adults Hospitalized for Acute Myocardial Infarction
Authors: Andrew J Arakaki, Rachel P Dreyer, Terrence Murphy, Katie Wang, Harlan M Krumholz, Yuan Lu, Philip Adejumo, Makoto Mori, Gail DONOFRIO, John Spertus, Judith H Lichtman
Journal: Circulation (2022)

Background: Perceived discrimination is associated with several risk factors for acute myocardial infarction (AMI), but little is known about the association between discrimination and health status outcomes post-AMI. Methods: We analyzed the 1- and 12-month health status of 2,670 young (≤ 55 years) adults recovering from an AMI enrolled in the VIRGO study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients). Perceived discrimination was assessed using the Everyday Discrimination Scale (EDS). General health status was measured using the Short Form 12 Physical and Mental Component Scores (PCS and MCS). Disease-specific health status was measured using the following domains of the Seattle Angina Questionnaire (SAQ): treatment satisfaction (TS), quality of life (QL) and dichotomous forms of the physical limitation and angina frequency domain scores (score &lt; 100). Lower scores indicate worse health status. Multivariable linear regression of the PCS, MCS, TS, and QL scores and multivariable logistic regression of the dichotomous forms of physical limitation and angina frequency were used to assess their adjusted associations with perceived discrimination. Results: Nearly 35.0% of the cohort reported discrimination (EDS &gt; 0). At 1-month post-AMI, increased EDS score was significantly associated with lower MCS, TS, and QL scores and higher odds of physical limitation and angina after adjustment (Figure) . At 12-months post-AMI, increased EDS score retained its significant associations with lower MCS and QL scores and higher odds of physical limitation and angina, but not its association with TS (Figure) . The EDS score was not associated with PCS at either 1- or 12-months post-AMI. Conclusions: Perceived discrimination was associated with worse mental health and disease-specific health status one year after AMI after adjusting important confounders. Further work to understand the source and how to mitigate perceived discrimination is needed.
Temporal trends in, and risk factors for, HIV seroconversion among female sex workers accessing Zimbabwe's national sex worker programme, 2009–19: a retrospective cohort analysis of routinely collected HIV testing data
Authors: Harriet S Jones, Bernadette Hensen, Sithembile Musemburi, Lilian Chinyanganya, Albert Takaruza, Sungai T Chabata, Primrose Matambanadzo, Lucy Platt, Brian Rice, Frances M Cowan, James R Hargreaves
Journal: The Lancet HIV (2023)

The frequency of new HIV infections among female sex workers in sub-Saharan Africa is poorly understood. We used routinely collected data that enable unique identification of repeat HIV testers to assess temporal trends in seroconversion and identify associated risk factors for female sex workers accessing Sisters with a Voice, Zimbabwe's national sex worker programme.
GOLD 2023 Executive Summary: responses from the GOLD Scientific Committee
Authors: Alvar Agustí, Antonio Anzueto, Bartolome R. Celli, Kevin Mortimer, Sundeep Salvi, Claus F. Vogelmeier
Journal: European Respiratory Journal (2023)

We thank the authors of the five letters received in relation to the recent publication of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 Executive Summary in the European Respiratory Journal [1] for their interest and insightful comments. We address them below, albeit necessarily briefly, under three categories: a global perspective, diagnostic issues, and management of exacerbations. The GOLD Scientific Committee respond to five letters to the Editor in relation to the GOLD 2023 Executive Summary <https://bit.ly/41wJzhk>
Abstract 9685: Pharmacodynamic and Pharmacokinetic Profiles of Switching Between Cangrelor and Ticagrelor Following Ticagrelor Pre-Treatment: The SWAP-5 Study
Authors: Luis G. Ortega-Paz, Fabiana Rollini, Mattia Galli, Latonya Been, Ghussan Ghanem, Awss shalhoub, Tiffany Ossi, Andrea Rivas, Xuan Zhou, Jose Rivas Rios, Andres Pineda, Siva Suryadevara, Daniel Soffer, Martin Zenni, Dominick J Angiolillo, Francesco Franchi
Journal: Circulation (2022)

Introduction: The lack of drug-drug-interaction (DDI) with the use of ticagrelor in cangrelor-treated patients was demonstrated in studies in which ticagrelor was given at the time of initiation or during cangrelor infusion. However, many patients are pre-treated with ticagrelor and to date there is no data to rule out a DDI when ticagrelor is given prior to starting cangrelor. Methods: SWAP-5 is a randomized, double-blind, placebo-controlled, cross-over, pharmacokinetic (PK) and pharmacodynamic (PD) study conducted in 20 patients with coronary artery disease on aspirin (81mg/qd). Patients were pre-treated with a 180-mg ticagrelor loading dose (LD) and after 1 hour were randomized to placebo or cangrelor (bolus and infusion for 2 hours). Patients crossed over after 1-4 weeks of washout. PK analysis included plasma levels of ticagrelor and its active metabolite, and PD assessments included VerifyNow P2Y 12 reaction units (PRU), light transmittance aggregometry (LTA) with 20 μM ADP as agonist, and vasodilator-stimulated phosphoprotein (VASP), at baseline and 6 time points after ticagrelor LD. Results: Compared to placebo, adding cangrelor to patients pre-treated with ticagrelor resulted in a significant reduction in PRU at 30 min and 1 hour after starting infusion ( Figure ). At 2 hours after stopping the infusion, PRU was low and similar in both groups (16.9 vs. 12.6; mean difference: 4.3; 95% CI: -28.6 to 37.3), meeting the non-inferiority primary endpoint (pre-defined non-inferiority margin 45 PRU). LTA and VASP showed consistent findings. PK tracked PD findings with no difference between groups in plasma levels of ticagrelor and its metabolite (data not shown). Conclusions: SWAP-5 is the first PK/PD study supporting the feasibility of adding cangrelor in patients pre-treated with ticagrelor. This approach resulted in lower levels of platelet reactivity during cangrelor infusion with similar PK/PD profiles after stopping the infusion and no evidence of DDI.
The coronavirus recombination pathway
Authors: Heather L. Wells, Cassandra M. Bonavita, Isamara Navarrete-Macias, Blake Vilchez, Angela L. Rasmussen, Simon J. Anthony
Journal: Cell Host & Microbe (2023)

Recombination is thought to be a mechanism that facilitates cross-species transmission in coronaviruses, thus acting as a driver of coronavirus spillover and emergence. Despite its significance, the mechanism of recombination is poorly understood, limiting our potential to estimate the risk of novel recombinant coronaviruses emerging in the future. As a tool for understanding recombination, here, we outline a framework of the recombination pathway for coronaviruses. We review existing literature on coronavirus recombination, including comparisons of naturally observed recombinant genomes as well as in vitro experiments, and place the findings into the recombination pathway framework. We highlight gaps in our understanding of coronavirus recombination illustrated by the framework and outline how further experimental research is critical for disentangling the molecular mechanism of recombination from external environmental pressures. Finally, we describe how an increased understanding of the mechanism of recombination can inform pandemic predictive intelligence, with a retrospective emphasis on SARS-CoV-2.
Early molecular layer interneuron hyperactivity triggers Purkinje neuron degeneration in SCA1
Authors: Federica Pilotto, Christopher Douthwaite, Rim Diab, XiaoQian Ye, Zahraa Al qassab, Christoph Tietje, Meriem Mounassir, Adolfo Odriozola, Aishwarya Thapa, Ronald A.M. Buijsen, Sophie Lagache, Anne-Christine Uldry, Manfred Heller, Stefan Müller, Willeke M.C. van Roon-Mom, Benoît Zuber, Sabine Liebscher, Smita Saxena
Journal: Neuron (2023)

Toxic proteinaceous deposits and alterations in excitability and activity levels characterize vulnerable neuronal populations in neurodegenerative diseases. Using in vivo two-photon imaging in behaving spinocerebellar ataxia type 1 (Sca1) mice, wherein Purkinje neurons (PNs) degenerate, we identify an inhibitory circuit element (molecular layer interneurons [MLINs]) that becomes prematurely hyperexcitable, compromising sensorimotor signals in the cerebellum at early stages. Mutant MLINs express abnormally elevated parvalbumin, harbor high excitatory-to-inhibitory synaptic density, and display more numerous synaptic connections on PNs, indicating an excitation/inhibition imbalance. Chemogenetic inhibition of hyperexcitable MLINs normalizes parvalbumin expression and restores calcium signaling in Sca1 PNs. Chronic inhibition of mutant MLINs delayed PN degeneration, reduced pathology, and ameliorated motor deficits in Sca1 mice. Conserved proteomic signature of Sca1 MLINs, shared with human SCA1 interneurons, involved the higher expression of FRRS1L, implicated in AMPA receptor trafficking. We thus propose that circuit-level deficits upstream of PNs are one of the main disease triggers in SCA1.
Labeling PIEZO2 activity in the peripheral nervous system
Authors: Nicholas W. Villarino, Yasmeen M.F. Hamed, Britya Ghosh, Adrienne E. Dubin, Amanda H. Lewis, Max A. Odem, Meaghan C. Loud, Yu Wang, M. Rocio Servin-Vences, Ardem Patapoutian, Kara L. Marshall
Journal: Neuron (2023)

Sensory neurons detect mechanical forces from both the environment and internal organs to regulate physiology. PIEZO2 is a mechanosensory ion channel critical for touch, proprioception, and bladder stretch sensation, yet its broad expression in sensory neurons suggests it has undiscovered physiological roles. To fully understand mechanosensory physiology, we must know where and when PIEZO2-expressing neurons detect force. The fluorescent styryl dye FM 1-43 was previously shown to label sensory neurons. Surprisingly, we find that the vast majority of FM 1-43 somatosensory neuron labeling in mice in vivo is dependent on PIEZO2 activity within the peripheral nerve endings. We illustrate the potential of FM 1-43 by using it to identify novel PIEZO2-expressing urethral neurons that are engaged by urination. These data reveal that FM 1-43 is a functional probe for mechanosensitivity via PIEZO2 activation in vivo and will facilitate the characterization of known and novel mechanosensory processes in multiple organ systems.
Five-year follow-up of KEYNOTE-087: pembrolizumab monotherapy for relapsed/refractory classical Hodgkin lymphoma
Authors: Philippe Armand, Pier Luigi Zinzani, Hun Ju Lee, Nathalie A. Johnson, Pauline Brice, John Radford, Vincent Ribrag, Daniel Molin, Theodoros P. Vassilakopoulos, Akihiro Tomita, Bastian von Tresckow, Margaret A. Shipp, Alex F. Herrera, Jianxin Lin, Eunhee Kim, Samhita Chakraborty, Patricia Marinello, Craig H. Moskowitz
Journal: Blood (2023)

Previous analyses of the phase 2 KEYNOTE-087 (NCT02453594) trial of pembrolizumab monotherapy demonstrated effective antitumor activity with acceptable safety in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL). However, long-term response durability and outcome of patients who receive a second course after treatment discontinuation after complete response (CR) remain of clinical interest. We present KEYNOTE-087 data after >5 years of median follow-up. Patients with R/R cHL and progressive disease (PD) after autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV; cohort 1), salvage chemotherapy and BV without ASCT (cohort 2), or ASCT without subsequent BV (cohort 3), received pembrolizumab for ≤2 years. Patients in CR who discontinued treatment and subsequently experienced PD were eligible for second-course pembrolizumab. Primary end points were the objective response rate (ORR) using blinded central review and safety. The median follow-up was 63.7 months. ORR was 71.4% (95% confidence interval [CI], 64.8-77.4; CR, 27.6%; partial response, 43.8%). Median duration of response (DOR) was 16.6 months; median progression-free survival was 13.7 months. A quarter of responders, including half of complete responders, maintained a response for ≥4 years. Median overall survival was not achieved. Among 20 patients receiving second-course pembrolizumab, ORR for 19 evaluable patients was 73.7% (95% CI, 48.8-90.8); median DOR was 15.2 months. Any-grade treatment-related adverse events occurred in 72.9% of patients and grade 3 or 4 adverse events occurred in 12.9% of patients; no treatment-related deaths occurred. Single-agent pembrolizumab can induce durable responses, particularly in patients achieving CR. Second-course pembrolizumab frequently reinduced sustained responses after relapse from initial CR.